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Global shifts in climate patterns and human land use practices have exacerbated the process of desertification in xeric grasslands of the continent. Although a formidable task to address these broad scale changes to grasslands, we use a bioindicator of the Southern Great Plains, the lesser prairie-chicken (Tympanuchus pallidicinctus) to deliver conservation triage. We outline an approach to improve the conservation of the prairies but perhaps save an imperiled species dependent upon such landscapes. We focus our efforts on removal of honey mesquite (Prosopis glandulosa) as one method to improve ecosystem function, but we use the ecology of the lesser prairie-chicken to target conservation efforts. We modeled the occurrence of lesser prairie-chicken leks (i.e., breeding arenas, n = 711 from 2002 to 2012) and quantify the areas that will likely provide the greatest ecological return on conservation investment. Our models indicated that lesser prairie-chickens exhibited strong avoidance in the presence of low density mesquite. Combining ecological response of the vegetation and species needs, we identify that treating low density mesquite provides the most cost-effective first step in addressing this threat to prairie-ecosystems. We suggest using bioindicator species could target conservation efforts to slow the tide of desertification in other regions of the globe. • Highlights of Slowing the tide of mesquite invasion: using a bioindicator species to deliver conservation triage. • Lesser prairie-chickens exhibited strong avoidance of low density mesquite. • Lesser prairie-chickens exhibited strong avoidance of uniformly distributed mesquite. • Treating low density mesquite is a cost-effective first step in prairie restoration. • These treatments may lead to larger ecosystem service benefits. [ABSTRACT FROM AUTHOR]